Fragile X drug trial gets $11.5 million in NIH funding

The UC Davis MIND Institute and Rush University Medical Center have been awarded $11.5 million from the National Institutes of Health to test a new therapy designed to improve language learning for children fragile X syndrome.

Randi Hagerman

Fragile X syndrome is a single-gene disorder and the most common inherited cause of intellectual disability, which can cause a range of learning disabilities and severe intellectual impairment. Fragile X syndrome is also the most commonly known single-gene cause of autism or autistic-like behaviors. Affecting one in 4,000 people worldwide, fragile X impairs a child’s ability to communicate.

“There is a great need to improve cognition early in development in fragile X syndrome, and this unique study combines a targeted treatment for this disorder with intensive language intervention,” said Randi Hagerman, the principal investigator for the study at UC Davis. “The randomized, double-blind study will examine if the drug AFQ056 can enhance neural plasticity in the form of language learning in young children with fragile X syndrome.”

Elizabeth Berry-Kravis, a study principal investigator and a pediatric neurologist at Rush, said the drug therapy could potentially improve language learning in young children with fragile X syndrome compared to just speech/language therapy alone.

“The drug targets a specific glutamate signaling problem in the brain of animal models with fragile X that is a direct result of the genetic defect,” she said. “In animal models it improves synaptic connections and signaling between neurons, with resultant effects on learning and memory.”

In the four-year study participants will either receive the drug therapy or a placebo for the initial period of about a year. Researchers hope to enroll 100 participants with fragile X syndrome between the ages of 32 months to six years.

All participants will be evaluated by speech-language therapists who will analyze and measure change in language skills in response to the intervention as well as deliver language therapy sessions to the family. Participants who receive the placebo and language therapy will be enrolled in the extension phase of the trial, in which all participants will be treated with the active drug.

The language therapy involves teaching parents strategies for promoting language growth in their children and delivered to parents in their homes through distance-video technology. Clinicians will support and coach parents in real time as they interact with their sons and daughters with fragile X syndrome.

In addition to determining whether the drug improves communication and learning in children with fragile X syndrome, the study will evaluate the drug’s safety and determine the most effective dose.

“The study will be the first of its kind to evaluate whether a treatment aimed at improving a core defect of brain connectivity in the disease can change the ability to learn in young children with fragile X syndrome,” said Berry-Kravis. “If successful this study could be a new model for development of medications that work directly on brain mechanisms in other genetic disorders affecting development and learning.”

Leonard Abbeduto, director of the UC Davis MIND Institute and co-leader of the research at UC Davis, said it will not only help participating families, but also change how the field conducts clinical trials of new drugs for people with intellectual and developmental disabilities.

The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health under award number U01NS096767.

The UC Davis MIND Institute in Sacramento, Calif., was founded in 1998 as a unique interdisciplinary research center where families, community leaders, researchers, clinicians and volunteers work together toward a common goal: researching causes, treatments and eventual preventions and cures for neurodevelopmental disorders. The institute has major research efforts in autism, fragile X syndrome, chromosome 22q11.2 deletion syndrome, attention-deficit/hyperactivity disorder (ADHD) and Down syndrome. More information about the institute and its Distinguished Lecturer Series, including previous presentations in this series, is available on the Web at mindinstitute.ucdavis.edu.